血小板衍生生长因子C(PDGF-C)是PDGF/VEGF(血管内皮生长因子)家族的成员,其中包括众所周知的对多种细胞类型有丝分裂作用的蛋白质。糖基化是翻译后修饰的最重要形式之一,其对分泌蛋白和膜蛋白具有显著影响。糖基化在促进蛋白质加工方面具有许多特征明确的作用,并有助于适当的折叠,构象,分布,和内质网(ER)和高尔基体细胞内合成的蛋白质的稳定性。虽然糖基化的一般过程和功能是有据可查的,还有很可能还有其他人被发现,因为许多潜在底物的糖基化尚未被表征。在这项研究中,我们报道PDGF-C蛋白在三个位点糖基化,包括Asn25、Asn55和Asn254。然而,我们发现这些位点的任何突变都不影响蛋白质的表达或分泌。同样,PDGF-C糖基化的破坏对其通过ER和高尔基体的进展没有影响。然而,在Asn254(N254A)处引入突变阻止了全长PDGF-C的激活及其通过PDGF受体的信号传导能力。我们的发现表明,糖基化影响PDGF-C的激活,而不是蛋白质的合成或加工。这项研究表征了PDGF-C蛋白的关键修饰,并可能为糖基化的过程和功能提供新的思路。
Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling via the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.